The PISA performance of Hong Kong has prompted this study to investigate if scientific literacy (SL) of Hong Kong students can be improved further through a high school biology course employing the STSE approach. A STSE course was developed in accordance to the contexts of Hong Kong and a framework for the assessment of scientific literacy was developed. Two classes of high school biology were selected for a quasi-experimental study: one taught with the STSE course and the other taught traditionally. Compared to the traditional class, the STSE approach produced better learning outcomes in: (i) application of scientific concepts, (ii) scientific inquiry skills, and (iii) STSE awareness, but showed no significant differences in recall of scientific concepts and attitudes toward science learning. The results show that a STSE approach of this study is feasible in an overtly exam-driven context of Hong Kong in light of its superiority in conceptual understanding over traditional teaching. But its impacts on NOS understanding and attitudes are found limited. The results have implications for science curriculum reforms in Hong Kong.